DOCSLIB.ORG

Somatotropic Dysfunction in Growth Hormone-Releasing Hormone-Deprived Neonatal Rats: Effect of Growth Hormone Replacement ~Hera~~'

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Somatotropic Dysfunction in Growth Hormone-Releasing Hormone-Deprived Neonatal Rats: Effect of Growth Hormone Replacement ~Hera~~' (M3 1 -3998/9413603-0315$03.o()/O PEDIATRIC RESEARCH Vol. 36. No. 3, 1994 Copyright O 1994 International Pediatric Research Foundation. Inc. Printed in U.S.A. Somatotropic Dysfunction in Growth Hormone-Releasing Hormone-Deprived Neonatal Rats: Effect of Growth Hormone Replacement ~hera~~' SILVANO G. CELLA, VITO DE GENNARO COLONNA, VITTORIO LOCATELLI, GILBERT0 E. BESTETTI, GIAN LUIGI ROSSI, ANTONIO TORSELLO, WILLIAM B. WEHRENBERG, AND EUGENIO E. MULLER Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, 20129 Milan, Italy [S.G. C., Kd. G.C., K L., A. T., E. E. M. I; Itutitlct fur Tierpathologie, Universitat Bern, CH-3001 Benz, Switzerland [G.E. B., G.L. R. I; Department of Health Sciences, University of Wisconsin, Milwaukee, Wisconsin 53201 [W. B. W. In a previous work, we reported that passive immunization than in normal rat serum-GH-treated pups, whereas the total with anti-growth hormone-releasing hormone (GHRH) anti- GH immunoreact~typer unit surface, an index of intracellu- bodies (GHRH-Ab) in neonatal rats caused disruption of so- lar hormone concentration, was slightly higher than in vehi- matotropic function that was still present 60 d posttreatment. cle-GH or GHRH-Ab pups. As determined by electron mi- We studied the reversibility of this condition by growth hor- croscopy, somatotropes from GHRH-Ab+GH pups had mone (GH) replacement therapy. Neonatal rats received morphologic features of high cellular activity. It appears that in GHRH-Ab (50 ~Urdt,s.c.) or normal rabbit serum every GHRH-deprived pups GH replacement therapy can normalize second day from birth up to postnatal d 10 and received hGH most but not all altered indices of the somatotropic function. (0.4 &g body weight, s.c., bid.) or vehicle in a 2 x 2 factorial The effects of GH are mainly directed at the pituitaly, whereas design. Animals were studied on d 11 of age. In GHRH-Ab- the sensitivity of the hypothalamus to GH replacement is treated rats, GH therapy 1) counteracted the reduced body lower. (PediatrRes 36: 315-322, 1994) weight and low plasma IGF-I levels; 2) failed to modify the reduced pituitary weight and GH content; 3) further reduced Abbreviations the low plasma GH levels; 4) partially restored the defective GH, growth hormone GH responsiveness to GHRH; 5) failed to modify the reduced GHRH, growth hormone-releasing hormone hypothalamic somatostatin and increased GHRH gene expres- GHRH-Ab, anti-GHRH-antibodies sion in the hypothalamus; and 6) reverted the decreased pitu- NRS, normal rabbit serum itary somatostatin binding. Morphologic and morphometric dCTP, deoxycytidine triphosphate evaluation of the pituitary gland from GHRH-Ab+GH pups PRL, prolactin showed that the number of GH-labeled structures was lower SS, somatostatin Recent studies by us (1,2) and by other groups (3,4) have It is presently unknown whether these changes are due to shown that rat pups treated with GHRH-Ab may represent a the GHRH deficiency itself or to the consequent reduction of suitable animal model for the study of the human growth GH secretion. Therefore, we studied the effects of concom- disorders caused by a primary hypothalamic dysfunction. itant GH and GHRH-Ab treatment. We have administered Neonatal administration of GHRH-Ab permanently inhibits GH daily to GHRH-deprived and control pups from postna- the growth rate and alters several indices of the hypophyseal tal d 1 to 10 and subsequently evaluated in vivo and in vitro somatotropic function (I). several hypothalamic and pituitary indices of somatotropic activity. Received November 11, 1993: accepted March 21, 1994. Correspondence and reprint requests: Eugenio E. Muller, MD. Department of METHODS Pharmacology. Chemotherapy and Toxicology. University of Milan, via Vanvi- telli 32. 20129 Milan. Italy. All procedures were reviewed and approved by the Supported by a grant from Kahi Pharmacia, Italy. 'This study was executed under the auspices of the Itallan Society of Endocri- ethical committee of the of Pharmaco'og~of nology. GH study Group. the University of Milan. Functional Studies group were collected in pools of three samples (four pools per experimental group), immediately frozen on dry ice, Animals. Pregnant Sprague-Dawley rats (Charles River, and stored at -70°C until used. Total RNA was obtained Calco, Italy) were purchased and housed under controlled by single-step acid guanidium-phenol-chloroform extrac- conditions (22 k TC, 65% humidity, and artificial light tion (9). Total RNA samples (20 pglsample) were elec- from 0600 to 2000 h). After birth, all litters were culled to trophoresed on 1.2% formaldehyde-agarose gel and a standard size of 12 pups and left with dams during the transferred to a nitrocellulose membrane (Schleicher & experimental period (see below). Studies were conducted Schuell, Dassel, Germany) at room temperature for 24 h on d 11 of age. In all, 250 pups were used. in 10 x SSC (1 x SSC = 0.1 M sodium chloridel0.01 M Antiserum to GHRH. The GHRH-Ab was prepared by sodium citrate). Filters were hybridized with a rat GH immunizing rabbits with a mixture of synthetic rat GHRH cDNA sequence kindly provided by Dr. Frances DeNoto (5) and methylated BSA emulsified in Freund's adjuvant, (University of California, San Francisco, CA). The probe as previously described (6). The biologic efficacy of the was labeled using the Megaprime DNA labeling system antiserum was assessed at various levels. The GHRH-Ab (Amersham, Little Chalfont, UK) with [a-"PI~CTP to a has repeatedly been shown to significantly inhibit GH sp act of 1 x 109 dpmlkg DNA. Control of the homoge- secretion and growth (3, 4, 7). In addition, the antiserum neity of the amount of RNA loaded was performed by was tested for rat GHRH-binding capacity with reprobing the filters with [a-3'~]d~~~-labeledP-actin labeled rat GHRH. The antiserum dilution required to cDNA. After hybridization, autoradiography was carried bind 30% of the tracer was approximately 1.30 000. Char- out at -70°C for 24 h in the presence of an intensifying acterization of the antiserum showed that it was directed screen using Hyperfil-MP (Amersham). Quantification of toward the GHRH carboxy terminal. It cross-reacted the hybridization signal was performed on a scanning with synthetic human, bovine, and porcine GHRH by densitometer (LKB XL Laser Densitometer, LKB, Upp- less than 4%, and the dose-response curves were not sala, Sweden). Pituitary GH mRNA levels were ex- parallel with rat GHRH. pressed as a percentage of the control values. The antiserum did not cross-react with peptides that Pituitary SS binding. The anterior pituitary glands of have considerable sequence homology with GHRH, in- seven pups for each experimental group were excised and cluding secretin, glucagon, vasoactive intestinal peptide, frozen in liquid nitrogen. The SS autoradiography was gastrin, motilin, bradykinin, and angiotensin. performed on 14-km-thick, slide-mounted frozen sec- Treatments. Each single litter was divided randomly tions as described by McCarthy and Plunkett (10). Due to into two groups, one of which was given GHRH-Ab (50 the limited amount of tissue, only two concentrations of ~Llrat,s.c.) starting on d 1 and then on d 2, 4, 6, 8, and ["'I]T~~'-SS(2000 Cilmmol, Amersham) were used. One 10; the other group was given equal amounts of NRS. was 0.4 nM, near the receptor k,, and the other was 0.8 Each group, in turn, was divided into two subgroups, nM, a saturating concentration for the receptors (11). which were given twice daily (at 0900 and 1900 h) hGH Nonspecific binding was determined with 10 pM unla- (Genotropin, Kabi Vitrum, Stockholm, Sweden, batch beled SS (Sigma Chemical Co., St. Louis, MO). Sections 870301, 0.4 kg/g body weight, LC.) diluted in normal were apposed to [3~]~yperfilm(Amersham), exposed for saline or equal amounts of normal saline from d 1 to 10. 3 d at -20"C, and quantified by using a computer-assisted All experiments were performed on d 11, at 0900 h, i.e. 14 image analyzer. The results were expressed in arbitrary h after the last GH injection. densitometry units. Eg'ct of acute GHRH. At 0830 to 0900 h, the free- Hypothalamic GHRH and SS gene expression. Hypotha- moving 11-d-old rats were injected with GHRH (human lami of the same pups used for pituitary GH mRNA GHRH-44, Sanofi, Paris, France, batch DADJOI) at the expression were collected. The ablated areas extended dose of 0.2 kg/kg body weight, S.C. and were killed 15 min from the optic chiasm to the mamillary bodies and later- later. Trunk blood was collected into EDTA-containing ally to the fornix. They were collected in pools of two tubes. Plasma samples and anterior pituitaries were samples, immediately frozen on dry ice, and stored at stored frozen until GH was determined by RIA, as pre- -70°C until used. The total RNA was isolated from viously described (8). In this study, about 50 pups were pooled hypothalamic tissue as alluded to previously (9). used. The total RNA samples (20 pglsample) were spotted onto IGF-I MA. Plasma IGF-I concentrations were evalu- nitrocellulose sheets (BA 85, 0.45 km, Schleicher & ated by a homologous RIA in plasma extracted with 2N Schuell; prewetted with 5 x SSC) using a slot-blot appa- HCI, 12.5%, plus 87.5% ethanol, using reagents provided ratus (Minifold 11, Schleicher & Schuell). Filters were by National Hormone and Pituitary Program (NHPP). hybridized with a rat GHRH cDNA (plasmid prGRF 2, The sensitivity of the assay was 100 pg/mL; intra- and kindly provided by Dr. Kelly E. Mayo, Northwestern interassay variabilities were less than 10%. The plasma University, Evanston, IL) and rat SS cDNA (plasmid levels of IGF-I of eight pups for each experimental group pSR-1, kindly provided by Dr.
Load more

Recommended publications
  • The Endocrine System Brightside July, 2019 by Dr
    The Endocrine System Brightside July, 2019 By Dr. Derek Conte How does the body regulate and balance itself from minute to minute, hour to hour and month to month? What is it that allows the food we eat to be utilized for growth, healing and energy? What causes the female egg to drop each month or a mother’s milk to flow? The answer is the endocrine system, which is comprised of the hypothalamus, pituitary gland, pineal gland, thyroid and parathyroid glands, thymus gland, the adrenals, pancreas, ovaries and testes. The brain signals these specialized glands to release hormones to initiate essential chemical actions that sustain life. The word “endocrine” literally means “to cry inside” and that is exactly what happens when the endocrine system works. An example is growth hormone (GH) or somatotropin, responsible for growth and tissue repair. During exercise or when we have low blood sugar or high blood amino acid levels, the hypothalamus leaks (“cries”) growth hormone releasing hormone (GHRH) through very small vessels into the anterior pituitary gland which then leaks growth hormone into the general circulation, acting on cells for growth or replacement of old or damaged tissues. Pro ballplayers looking for an edge have been using growth hormone. The hormone that shuts this process off is called growth hormone inhibiting hormone (GHIH) or somatostatin (“growth stop”), released when blood sugar levels are high. If there ever is an excess of growth hormone, it can result in gigantism or acromegaly depending on whether its onset occurred before or after the growth plates in the bones have closed around the age of 17.
    [Show full text]
  • Growth Hormone Booklet
    GROWTH HORMONE AND PRADER-WILLISECOND EDITION SYNDROME A REFerence For FaMILies and Care ProViders Donald G. Goranson, Jr., Editor Growth Hormone and Prader-Willi Syndrome — Second Edition Published By: Prader-Willi Syndrome Association (Usa) 8588 Potter Park Drive, Suite 500 Sarasota, Florida 34238 Toll Free: 800-926-4797 Local: 941-312-0400 Fax: 941-312-0142 www.pwsausa.org © Copyright 2011 A Reference for Families and Care Providers Growth HORMONE AND PraderSECOND-WILLI EDITION Syndrome A REFerence For FaMILies and Care ProViders Donald G. Goranson, Jr., Editor Growth Hormone and Prader-Willi Syndrome — Second Edition A Reference for Families and Care Providers CONTENTS Acknowledgments....................................................................... 5 Introduction and History .............................................................. 7 Prader-Willi Syndrome and Growth ...................................................... 9 Effects of Growth Hormone Treatment in Children with PWS ................................ 20 What Is Involved in Growth Hormone Treatment? .......................................... 26 Questions, Wisdom and Survey Data from our Families ..................................... 34 Appendix: A. Overview of Prader-Willi Syndrome................................................ 40 B. Information Resources on Prader-Willi Syndrome .................................... 42 C. Information Resources on Growth Hormone Use and Products ........................ 43 D. Glossary of Terms ............................................................
    [Show full text]
  • Growth and Growth Hormone I
    Pediat. Res. 2: 43-63 (1968) Dwarfism, constitutional hypoglycemia dwarfism, psychosocial insulin gonadal dysgenesis maternal depriva- growth hormone tion syndrome growth retardation panhypopituitarism Growth and Growth Hormone I. Changes in Serum Level of Growth Hormone Following Hypoglycemia in 134 Children with Growth Retardation S.L.KAPLAN, C.A.L.ABRAMS, J.J.BELL, F.A.CONTE and M.M.GRUMBACH[41] Department of Pediatrics, University of California, San Francisco Medical Center, San Francisco, California, and College of Physicians and Surgeons, Columbia University, New York, New York, USA Extract The change in levels of growth hormone in serum (SGH) following insulin-induced hypoglycemia was evaluated in 134 prepubertal children with growth retardation and 10 control subjects with normal growth patterns by radioimmunoassay, utilizing 131I-HGH and rabbit antiserum to human growth hormone. Mean maximum growth hormone concentration (m^g/ml) at any time during the test was: 10 Control subjects 12.4 53 Hypopituitarism 2.5 m^g or less in 52/53 20 Constitutional shortness of stature 12.5 22 Primordial dwarfism 12.1 9 XO gonadal dysgenesis 13.4 5 Delayed adolescence 11.8 5 Maternal deprivation 16.7 9 Psychosocial dwarfism 10.9 11 Miscellaneous disorders 7.0 Among factors found to affect the SGH response to insulin-induced hypoglycemia were: a) elevated fasting concentration of SGH which appeared to alter the responsiveness to stimulation; and b) age. The mean maximum SGH concentration of the control subjects following insulin-induced hypo- glycemia was 12.4 m^Mg/ml. In 52/53 patients with hypopituitarism, the SGH concentration was 1 m/*g or less at rest, with no increase or an increase to a maximum of 2.5 m^Mg/ml following hypoglycemia.
    [Show full text]
  • HORMONES and SPORT Insulin, Growth Hormone and Sport
    13 HORMONES AND SPORT Insulin, growth hormone and sport P H Sonksen Guy’s, King’s and St Thomas’ School of Medicine, St Thomas’ Hospital, London SE1 7EH, UK; Email: [email protected] Abstract This review examines some interesting ‘new’ histories of blood rather than urine samples. The first method has a insulin and reviews our current understanding of its window of opportunity lasting about 24 h after an injec- physiological actions and synergy with GH in the regu- tion and is most suitable for ‘out of competition’ testing. lation of metabolism and body composition. It reviews the The second method has reasonable sensitivity for as long as history of GH abuse that antedates by many years the 2 weeks after the last injection of GH and is uninfluenced awareness of endocrinologists to its potent anabolic actions. by extreme exercise and suitable for post-competition Promising methods for detection of GH abuse have been samples. This method has a greater sensitivity in men than developed but have yet to be sufficiently well validated to in women. The specificity of both methods seems accept- be ready for introduction into competitive sport. So far, ably high but lawyers need to decide what level of there are two promising avenues for detecting GH abuse. scientific probability is needed to obtain a conviction. Both The first uses immunoassays that can distinguish the methods need further validation before implementation. isomers of pituitary-derived GH from the monomer of Research work carried out as part of the fight against recombinant human GH. The second works through doping in sport has opened up a new and exciting area of demonstrating circulating concentrations of one or more endocrinology.
    [Show full text]
  • Secretin and Autism: a Clue but Not a Cure
    SCIENCE & MEDICINE Secretin and Autism: A Clue But Not a Cure by Clarence E. Schutt, Ph.D. he world of autism has been shaken by NBC’s broadcast connections could not be found. on Dateline of a film segment documenting the effect of Tsecretin on restoring speech and sociability to autistic chil- The answer was provided nearly one hundred years ago by dren. At first blush, it seems unlikely that an intestinal hormone Bayless and Starling, who discovered that it is not nerve signals, regulating bicarbonate levels in the stomach in response to a but rather a novel substance that stimulates secretion from the good meal might influence the language centers of the brain so cells forming the intestinal mucosa. They called this substance profoundly. However, recent discoveries in neurobiology sug- “secretin.” They suggested that there could be many such cir- gest several ways of thinking about the secretin-autism connec- culating substances, or molecules, and they named them “hor- tion that could lead to the breakthroughs we dream about. mones” based on the Greek verb meaning “to excite”. As a parent with more than a decade of experience in consider- A simple analogy might help. If the body is regarded as a commu- ing a steady stream of claims of successful treatments, and as a nity of mutual service providers—the heart and muscles are the pri- scientist who believes that autism is a neurobiological disorder, I mary engines of movement, the stomach breaks down foods for have learned to temper my hopes about specific treatments by distribution, the liver detoxifies, and so on—then the need for a sys- seeing if I could construct plausible neurobiological mechanisms tem of messages conveyed by the blood becomes clear.
    [Show full text]
  • Regulatory Mechanisms of Somatostatin Expression
    International Journal of Molecular Sciences Review Regulatory Mechanisms of Somatostatin Expression Emmanuel Ampofo * , Lisa Nalbach, Michael D. Menger and Matthias W. Laschke Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany; [email protected] (L.N.); [email protected] (M.D.M.); [email protected] (M.W.L.) * Correspondence: [email protected]; Tel.: +49-6841-162-6561; Fax: +49-6841-162-6553 Received: 25 May 2020; Accepted: 9 June 2020; Published: 11 June 2020 Abstract: Somatostatin is a peptide hormone, which most commonly is produced by endocrine cells and the central nervous system. In mammals, somatostatin originates from pre-prosomatostatin and is processed to a shorter form, i.e., somatostatin-14, and a longer form, i.e., somatostatin-28. The two peptides repress growth hormone secretion and are involved in the regulation of glucagon and insulin synthesis in the pancreas. In recent years, the processing and secretion of somatostatin have been studied intensively. However, little attention has been paid to the regulatory mechanisms that control its expression. This review provides an up-to-date overview of these mechanisms. In particular, it focuses on the role of enhancers and silencers within the promoter region as well as on the binding of modulatory transcription factors to these elements. Moreover, it addresses extracellular factors, which trigger key signaling pathways, leading to an enhanced somatostatin expression in health and disease. Keywords: somatostatin; pre-prosomatostatin; δ-cells; central nervous system (CNS); gut; hypothalamus; cAMP resonse element (CRE); pancreas/duodenum homeobox protein (PDX)1; paired box protein (PAX)6; growth hormone (GH); brain-derived neurotrophic factor (BDNF); glutamateric system; pancreas 1.
    [Show full text]
  • Hypothalamic-Pituitary Axes
    Hypothalamic-Pituitary Axes Hypothalamic Factors Releasing/Inhibiting Pituitary Anterior Pituitary Hormones Circulating ACTH PRL GH Hormones February 11, 2008 LH FSH TSH Posterior Target Pituitary Gland and Hormones Tissue Effects ADH, oxytocin The GH/IGF-I Axis Growth Hormone Somatostatin GHRH Hypothalamus • Synthesized in the anterior lobe of the pituitary gland in somatotroph cells PITUITARY • ~75% of GH in the pituitary and in circulation is Ghrelin 191 amino acid single chain peptide, 2 intra-molecular disulfide bonds GH Weight; 22kD • Amount of GH secreted: IGF-I Women: 500 µg/m2/day Synthesis IGF- I Men: 350 µg/m2/day LIVER Local IGF-I Synthesis CIRCULATION GH Secretion: Primarily Pulsatile Pattern of GH Secretion Regulation by two hypothalamic in a Healthy Adult hormones 25 Sleep 20 Growth - SMS Hormone 15 Somatostatin Releasing GHRH + GH (µg/L) Hormone Inhibitory of 10 Stimulatory of GH Secretion GH Secretion 05 0 GHRH induces GH Somatostatin: Decreases to allow 0900 2100 0900 synthesis and secretion Clocktime GH secretory in somatotrophs Bursts GH From: “Acromegaly” by Alan G. Harris, M.D. 1 Other Physiological Regulators of GH Secretion Pharmacologic Agents Used to Stimulate GH Secretion Amino Sleep Exercise Stress Acids Fasting Glucose Stimulate hypothalamic GHRH or Inhibit Somatostatin Hypothalamus GHRH SMS Hypoglycemia(Insulin) Pituitary L-dopa Arginine Clonidine GHRH + - SMS Pyridostigmine GH Target Tissues Metabolic & Growth Promoting GH Effects IGF-I Insulin-like growth factor I (IGF-I) Major Determinants of Circulating
    [Show full text]
  • Plasma Somatostatin and Cholecystokinin Levels in Preterm Infants and Their Mothers at Birth
    0031-399819513706-0771$03.0010 PEDIATRIC RESEARCH Vol. 37, No. 6, 1995 Copyright O 1995 International Pediatric Research Foundation, Inc Printed in U.S.A. Plasma Somatostatin and Cholecystokinin Levels in Preterm Infants and Their Mothers at Birth C.-J. TORNHAGE, F. SERENIUS, K. UVNAS-MOBERG,AND T. LINDBERG Department of Pediatrics, UmeB University, UmeB [C.-J.T., F.S., T.L.] and Department of Pharmacology, Karolinska Institute, Stockholm, Sweden [K. U-M.] Regulatory gut peptides play an important role in regulating same. They were also independent of sex, birth weight, gesta- the gastrointestinal tract. Our knowledge about the pattern of tional age, umbilical cord blood pH, or glucose level. In mothers, secretion and function of these peptides is scanty in preterm but not in infants, plasma SS levels were higher after vaginal infants. Therefore, plasma somatostatin (SS) and cholecystokinin delivery than after cesarean section. After multiple birth, new- (CCK) levels were estimated just after birth in 65 mothers and 73 born plasma SS, but not plasma CCK, was significantly lower preterm infants (umbilical cord blood). The gestational age was than after single birth (9.1 + 7.7 versus 16.9 2 12.7 pmol/L). 32 (24-36 median ranges) wk and birth weight 1900 (475-3350) (Pediatr Res 37: 771-776, 1995) g. The umbilical cord blood pH was 7.32 + 0.10 (mean t- SD). After Sep-Pak-C,, semichromatography of plasma, SS and CCK Abbreviations were analyzed by RIA. Both plasma SS and CCK levels were SS, somatostatin significantly higher in infants than in mothers (SS = 14.5 i.
    [Show full text]
  • Influence of the Endocrine System on Growth and Development R
    331. INFLUENCE OF THE ENDOCRINE SYSTEM ON GROWTH AND DEVELOPMENT R. J. GERRITS A. R. S., U. S. D. A. Introduction The field of endocrinology cannot be defined in a manner entirely acceptable to all biologists or animal scientists. This is understandable as there are many points of view and many voids in our knowledge in this area. It is very hard to give a precise definition for an endocrine gland because all cells possess some secretory capacity and therefore contribute to the internal environment of the organism. For the most part the term "hormone" is probably applied too loosely and to a great variety of unrelated substances. Hormones can be identified as chemical agents which are synthesized by circumscribed parts of the body, generally specialized ductless glands, and are carried by the circulatory system to another part of the body where they evoke systemic adjustments by acting on rather specific target tissues or organs (Turner, 1966). In general, hormones regulate many processes such as growth, regeneration, reproduction, blood chemistry, metabolic rate, etc. Hormones act on the organs and tissues of the body by regulating the rate of specific metabolic reactions without contributing much at all to the constituent cell. It can be said that ad- justments to hormone levels require duration rather than speed, as opposed to the rapid coordinations of the body that are controlled by the nervous system. These biochemical adjustments are accomplished at the cellular level by virtue of their power to augwnt or restrain special enzyme sys- tems. It is important that hormones be released at the right time and in the proper amounts of the normal organism if they are to accomplish their specific mission.
    [Show full text]
  • Human Growth Hormone: Endogenous Production and Lifelong Health Benefits
    Human Growth Hormone: Endogenous Production and Lifelong Health Benefits Jason D. Martinez Advisor: Robert Davidson, Ph.D. November 29, 2012 Abstract Objective: To present a clear explanation of the purpose of Human Growth Hormone (hgH). Inform the reader of ways to naturally increase hgH. Increase awareness as to what benefits this hormone holds. Decrease the negative connotation surrounding hgH. Methods: Published literature on the topic of Human Growth Hormone (hgH) was collected and reviewed. Search subjects included, but were not limited to, endogenous production of hgH, nutritional considerations, and the effects of exercise on production of hgH. Results: An increase in endogenous secretion elicits a greater capacity for cell regeneration. Deep sleep is one of the highest yielding states for our bodies to be in for the production of the hormone. Some studies have shown that modifications of diet and exercise can push hgH production to it’s limits. Unfortunately, it is almost impossible to detect exogenous sources with current drug testing methods. Conclusions: In light of the medicinal use of human growth hormone (hgH) there are many other ways we can utilize the benefits surrounding this substance. Short wave sleep patterns, as well as good nutrition is an important diurnal approach to exogenous production of the hormone. The amino acid leucine holds a very important secondary role in the longevity of hgH in the blood by decreasing oxidation of the hormone. Lastly, intense exercise that requires forced and negative repetition training also invokes an enormous response of acute stress which in turn requires the central nervous system to boost production.
    [Show full text]
  • Regulation of CRH-Induced Secretion of ACTH and Corticosterone By
    European Journal of Endocrinology (2005) 153 R7–R10 ISSN 0804-4643 RAPID COMMUNICATION Regulation of CRH-induced secretion of ACTH and corticosterone by SOM230 in rats A P Silva, P Schoeffter, G Weckbecker, C Bruns and H A Schmid Novartis Institutes for BioMedical Research, Basel, Switzerland (Correspondence should be addressed to H Schmid; Email: [email protected]) Abstract Objective: Adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome is biochemically characterized by increased plasma concentrations of ACTH inducing hypersecretion of cortisol. Somatostatin is known to inhibit ACTH secretion, and in vitro data have shown the inhibition of ACTH secretion by agonists activating sst2 and sst5 receptors. The present study aimed to determine the inhibitory effect of the multireceptor ligand SOM230, compared with the sst2-preferring agonist octreotide, on corticotropin-releasing hormone (CRH)-stimulated secretion of ACTH and corticoster- one in rats. Methods: Secretion of ACTH and corticosterone was induced by i.v. application of CRH (0.5 mg/kg) in rats pretreated 1 h before by i.v. application of SOM230 (1, 3, or 10 mg/kg), octreotide (10 mg/kg) or NaCl 0.9%. Results: SOM230 (3 and 10 mg/kg) inhibited CRH-induced ACTH release by 45^3% and 51^2%, respectively, and corticosterone release by 43^5% and 27^16%, respectively. 10 mg/kg of octreotide tended to be less potent at inhibiting ACTH release (34^6% inhibition) and did not alter the secretion of corticosterone. Conclusion: SOM230 has a stronger inhibitory effect on ACTH and corticosterone secretion than octreotide in rats. This difference can be explained by its higher affinity to sst1, sst3 and especially sst5 receptors compared with octreotide.
    [Show full text]
  • Growth Hormone-Releasing Hormone in Lung Physiology and Pulmonary Disease
    cells Review Growth Hormone-Releasing Hormone in Lung Physiology and Pulmonary Disease Chongxu Zhang 1, Tengjiao Cui 1, Renzhi Cai 1, Medhi Wangpaichitr 1, Mehdi Mirsaeidi 1,2 , Andrew V. Schally 1,2,3 and Robert M. Jackson 1,2,* 1 Research Service, Miami VAHS, Miami, FL 33125, USA; [email protected] (C.Z.); [email protected] (T.C.); [email protected] (R.C.); [email protected] (M.W.); [email protected] (M.M.); [email protected] (A.V.S.) 2 Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33101, USA 3 Department of Pathology and Sylvester Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33101, USA * Correspondence: [email protected]; Tel.: +305-575-3548 or +305-632-2687 Received: 25 August 2020; Accepted: 17 October 2020; Published: 21 October 2020 Abstract: Growth hormone-releasing hormone (GHRH) is secreted primarily from the hypothalamus, but other tissues, including the lungs, produce it locally. GHRH stimulates the release and secretion of growth hormone (GH) by the pituitary and regulates the production of GH and hepatic insulin-like growth factor-1 (IGF-1). Pituitary-type GHRH-receptors (GHRH-R) are expressed in human lungs, indicating that GHRH or GH could participate in lung development, growth, and repair. GHRH-R antagonists (i.e., synthetic peptides), which we have tested in various models, exert growth-inhibitory effects in lung cancer cells in vitro and in vivo in addition to having anti-inflammatory, anti-oxidative, and pro-apoptotic effects. One antagonist of the GHRH-R used in recent studies reviewed here, MIA-602, lessens both inflammation and fibrosis in a mouse model of bleomycin lung injury.
    [Show full text]